Single-modality endocrine therapy versus radiation therapy after breast-conserving surgery in women aged 70 years and older with luminal A-like early breast cancer (EUROPA): preplanned interim analysis of a phase 3 non-inferiority randomized trial

<p dir="ltr"><b>Background </b>Optimal therapy following breast-conserving surgery (BCS) in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial is a non-inferiority, phase 3 randomized study designed to compare the effects of radiation therapy (RT) and endocrine therapy (ET) as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population.</p><p dir="ltr"><b>Methods</b> Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone BCS and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomized 1:1 to receive single-modality ET or RT. ET consisted of daily oral aromatase inhibitors or tamoxifen, while RT was administered as either whole breast or partial breast irradiation, delivered in 5 to 15 fractions. Randomization was stratified by G8 health status and age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the EORTC QLQ-C30 at 24 months, and 5-year IBTR rates. This interim analysis reports results for the HRQOL endpoint based on data from 152 patients who completed the 24-month assessment. The study is ongoing and actively recruiting (ClinicalTrials.gov, NCT04134598).</p><p dir="ltr"><b>Findings</b> Between March 4, 2021, and June 14, 2024, 731 women were randomized to receive RT (n=365) or ET (n=366). This analysis included 104 patients in the RT arm and 103 in the ET arm, predominantly Caucasian (98%), with a median follow-up of 23·9 months (IQR 22·9–24·2). The mean baseline GHS score was 71·9 (SD 19·05) in the RT and 75·5 (SD 19·34) in the ET arm. At 24 months, GHS scores declined by -1·1 in the RT and -10·0 in the ET arm, with an age- and G8 score-adjusted mean difference of 6·39 favouring RT (95% CI 0·14 to 12·65; p=0·0453). Treatment-related adverse events (AEs) were less frequent in the RT (65 [67%]) compared to the ET arm (76 [85·4%]). The most common grade 1–2 AEs were breast pain (37 [38·1%]), fatigue (32 [33%]), and arthralgia (28 [28·9%]) in the RT arm, and arthralgia (62 [69·7%]), fatigue (40 [44·9%]), and hot flashes (29 [32·6%]) in the ET arm. The most frequent grade 3–4 AE was arthralgia in the ET arm (6 [6·7%]). Serious AEs were reported in 15 patients (15·5%) in the RT arm and 13 (14·6%) in the ET arm.</p><p dir="ltr"><b>Interpretation</b> ET was associated with a greater reduction in HRQOL GHS compared to RT at 24 months. While these interim results suggest RT may better preserve HRQOL in older women with low-risk early breast cancer, further data on disease control outcomes and final patient accrual are needed to draw definitive conclusions.</p>